AB0121 STUDY OF SLAMF7 EXPRESSION IN PRIMARY GOUGEROT-SJÖGREN SYNDROME
Authors: C. Schleiss, R. Felten, F. Monneaux, H. Dumortier, J.E. Gottenberg
Journal: Annals of the Rheumatic Diseases (2022)

<h3>Background</h3> SLAMF7 (CD319, CS1) is a lymphocyte signaling activation molecule (SLAM) belonging to the CD2 receptor family. It regulates many immune functions following its activation by homotypic interaction (SLAMF7 as ligand and receptor). Its expression is observed on different hematopoietic cells such as plasma cells and NK cells and its activation leads to increased cytotoxic degranulation and IFNg secretion. SLAMF7 is a therapeutic target in multiple myeloma where plasma cells over-express SLAMF7. Elotuzumab, which binds to SLAMF7, induces an antibody-mediated cytotoxicity mechanism and an increase in the anti-tumor activity of NK cells. <h3>Objectives</h3> We investigated SLAMF7 expression in primary Sjögren's syndrome (pSS). <h3>Methods</h3> SLAMF7 expression was studied using flow cytometry on different subpopulations (CD4 T cells, CD8 T cells, NK cells, plasma cells (CD19+ CD38+ CD27high) and naive (CD27-) or mature (CD27+) B cells before (IgD+) or after (IgD-) class switching in pSS patients and healthy donors (HD). SLAMF7 protein expression was measured by the difference in expression (condition with antibody recognizing SLAMF7 - condition without antibody) of the mean fluorescence intensity (delta MFI). <h3>Results</h3> The pSS cohort consisted of 18 patients (17 women). 71% of patients were anti-SSA+, 41% anti-SSB+, 44% had rheumatoid factors (RF). The median IgG level was 13.3 g/l (9.88-21.45). 8/18 patients had evidence of systemic activity (ESSDAI score &gt;0). Twenty-one healthy donors (19 women) were used as controls. No overall difference in SLAMF7 expression was observed between pSS and healthy donors, or among pSS patients between patients with or without systemic complications. SLAMF7 expression was higher in patients with than in patients without autoantibodies or markers of B-cell activation. 1/RF-positive patients had a higher expression of SLAMF7 than RF-negative patients by IgD- CD27+ B cells (median delta MFI: 397 for RF+ pSS vs 185 for RF- negative pSS [p=0.001] vs 187 [p&lt;0.0001] for HD) and by C27+ IgD+ B cells (median delta MFI: 450 for RF+ pSS vs 307 for RF- negative pSS [p=0.005] vs 329 [p=0.001] for HD). 2/ Anti-SSA-positive patients had a higher expression of SLAMF7 than anti-SSA-negative patients by CD27+ IgD- B cells (median delta MFI: 346 for anti-SSA+ pSS vs 149 for anti-SSA-negative pSS [p=0.019] vs 187 [p=0.007] for HD) and by C27+ IgD+ B cells (median delta MFI: 403 for anti-SSA+ pSS vs 264 for anti- SSA negative pSS [p=0.021] vs 329 [p=0.012] for HD). The same association with a higher expression of SLAMF7 was observed for anti-SSB. 3/SLAMF7 expression was correlated with IgG levels in pSS patients on IgD- CD27+ B cells (r=0.51, p=0.044). <h3>Conclusion</h3> This study shows for the first time an overexpression of SLAMF7 on the surface of mature B cells in patients with pSS. This overexpression of SLAMF7 is associated with the presence of markers of B-cell activation. The therapeutic targeting of SLAMF7 therefore deserves further investigation in pSS. A study of its expression in the target tissue of the disease, minor accessory salivary glands, will allow a more precise analysis of the potential pathogenic role of SLAMF7 in pSS. <h3>Acknowledgements</h3> Necessity project <h3>Disclosure of Interests</h3> None declared